Experiments are being performed in rats to determine how a new peripheral nerve segment develops in a silicone tube. We believe the nerve formation in an artificial tube exaggerates the events at a nerve anastomosis site in that they occur over a longer distance and time. Studies are in progress to analyze the early cellular events that take place during the initial tissue cable formation and axonal regeneration. We have prepared cables which, by light microscopy, have demonstrated that cells migrate from both ends of nerve stumps inserted into opposite ends of a 14 mm long tube. Our focus of interest was to find a time at which migrating cells had not yet met in the middle of the tube. We are now performing an electron microscopic analysis of the growing tips of axons in relation to the nonneuronal cells (e.g., Schwann cells) and matrix in the cable. We have continued our studies on the development and regeneration of the permeability barriers of nerve. Previously, we found that whereas the endoneurial blood-nerve barrier (BNB) of normal and in situ regenerated nerve is impermeable to the vascular tracer horseradish peroxidase (HRP), the BNB of nerve segments in tubes is not. However, during the early phases of nerve degeneration and regeneration in situ, there is a marked increase in BNB permeability. Accordingly, we have begun to examine crushed and cut nerves in rats to elucidate the cause and initiating event of the increased vascular permeability. We found by light microscopy that, within 1-2 weeks, injured nerves are permeable to HRP. It is of interest that we did not see blood-borne cells migrating through vascular walls, which might have accounted for the increased HRP permeability. An electron microscopic investigation is in progress to determine the route of HRP passage through the endothelium of the endoneurial blood vessels. In a collaborative project, we have studied the effect of chronic implantation and stimulation of microelectrodes on the visual cortex of a monkey. Neuronal loss was minimal. The pia mater and astocytic foot processes reacted to ensheath the microelectrodes, isolating them from the surrounding nervous tissue. The stimulated but not unstimulated electrodes elicited a macrophage reaction that included some giant cells. We feel that the pathology observed is not severe enough to contraindicate the use of our visual prosthesis in blind people.